SUMMARY Parkinson's disease (PD) is a debilitating neurodegenerative disease that affects about 1-2% of the population over the age of 60. The pathological hallmark of PD is the presence of intracellular protein aggregates that cause the degeneration and then death of dopaminergic neurons in the substantia nigra. The presynaptic protein ?-synuclein was found to be the main component of Lewy bodies and ?-synuclein aggregation is believed to be the key event in PD pathogenesis. Past drug discovery efforts have been focused on preventing ?-synuclein aggregation or increasing ?-synuclein clearance. However, overexpression and knockdown studies in cell lines and animal models showed that altering intracellular ?-synuclein protein levels can also regulate PD pathology. These results suggest that ?-synuclein translation is a significant yet under explored target for PD drug discovery. A putative iron-responsive element (IRE) that exhibited high sequence and structural similarities with the ferritin IRE was found in the distal 5'-untranslated region of ?-synuclein mRNA and studies suggest that this IRE plays a critical role in regulating ?-synuclein translation. Thus far, there is no high-throughput drug discovery methods that can interrogate drug binding directly to RNA structures that control protein translation. This is needed to bypass artifact-prone protein reporters that are typically used to study translation inhibitors. Therefore, this phase I SBIR application aims to develop a fluorescence sensor that monitors drug binding to IREs and can enable high-throughput drug screens for compounds that specifically target ?-synuclein's IRE and ultimately result in lead compounds that could eventually be developed into inhibitor of ?-synuclein protein synthesis.